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Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 19, International Journal of Molecular Sciences, Vol 21, Iss 7237, p 7237 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI, 2020.
-
Abstract
- Maternal chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (n = 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.
- Subjects :
- 0301 basic medicine
asymmetric dimethylarginine
uremic toxin
trimethylamine-N-oxide
renin-angiotensin system
030204 cardiovascular system & hematology
Gut flora
lcsh:Chemistry
Fetal Development
chemistry.chemical_compound
0302 clinical medicine
Pregnancy
Medicine
lcsh:QH301-705.5
Spectroscopy
biology
General Medicine
Computer Science Applications
Prenatal Exposure Delayed Effects
Gestation
Female
Maternal Inheritance
medicine.medical_specialty
hypertension
Offspring
short chain fatty acid
Nitric Oxide
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Internal medicine
developmental origins of adult health and disease (DOHaD)
Animals
Physical and Theoretical Chemistry
Renal Insufficiency, Chronic
Molecular Biology
Fetus
gut microbiota
business.industry
Adenine
Organic Chemistry
medicine.disease
biology.organism_classification
Gastrointestinal Microbiome
Rats
Disease Models, Animal
030104 developmental biology
Endocrinology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Dysbiosis
business
Asymmetric dimethylarginine
chronic kidney disease
Kidney disease
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 21
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....05a15eb7e42a3b01d82d7cc04681e4d0